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本文总结了在马拉维北部卡龙加区超过30年结核病(TB)研究情况,是此地区多数非洲农村的代表了。一个突出的因素是人类免疫缺陷病毒(HIV),约在1980年在此地区出现,导致结核病发病率上升,在2000年达到高峰(涂阳肺结核发病率65/10万)。结核菌素调查显示结核分枝杆菌年感染率接近1%;因此多数人未感染,并且处于原发感染和发病的危险中。分子流行病学研究证明约2/3结核病例源于近期感染,但是可识别的近期接触仅是形成10%病例的原因。截至2001年,57%结核病患者可直接归因于HIV感染,暗示着如果不是由于HIV感染,结核病发病率可能下降。HIV感染增加了大多数青壮年患结核病的风险,并显著增加了治疗后新感染复发的风险。HIV感染者中的死亡率很高,但是HIV感染与耐药无关联。其他影响相对较弱的危险因素包括年龄、性别、接触、几个遗传多态性和区域。1个或2个剂量卡介苗(BCG)对成人肺结核无保护作用,尽管对麻风病有保护作用。与英国合作开展的皮肤试验调查、队列研究和对比免疫学研究显示暴露于环境分枝杆菌能提供针对结核病的保护,卡介苗无效部分归于这些掩盖疫苗效果的广泛异源性暴露。耐药水平在过去的20多年保持不变(<10%)。用母牛分枝杆菌进行免疫治疗不能提供保障,但是用复方新诺明治疗HIV阳性患者能降低死亡率。卡龙加项目阐明了长期以人群为基础的研究对于调查结核病的自然史,以及影响结核病控制政策的价值。目前的研究集中于感染、疾病和保护的免疫学标记物,集中于阐明在人群水平抗逆转录病毒治疗对于结核病发病的效果。
This paper summarizes the more than 30-year history of tuberculosis (TB) research in Kalunga district in northern Malawi and represents most of the rural areas of Africa in this region. A prominent factor was the human immunodeficiency virus (HIV), which appeared in the area around 1980, leading to an increase in the incidence of tuberculosis, which peaked in 2000 (the incidence of smear-positive pulmonary tuberculosis is 65/10 million). Tuberculin surveys show that the annual infection rate of M. tuberculosis is close to 1%; thus most people are uninfected and at risk of primary infection and morbidity. Molecular epidemiological studies show that about two-thirds of tuberculosis cases result from recent infections, but identifiable recent contacts are only the cause of 10% of cases. As of 2001, 57% of TB patients were directly attributable to HIV infection, suggesting that the incidence of tuberculosis may decline if not due to HIV infection. HIV infection increases the risk of tuberculosis in most young adults and significantly increases the risk of recurrence of new infections after treatment. Mortality among HIV-infected persons is high, but HIV infection is not associated with resistance. Other risk factors that are relatively less affected include age, gender, exposure, several genetic polymorphisms and regions. One or two doses of BCG have no protective effect against tuberculosis in adults, despite protection against leprosy. Skin tests conducted in collaboration with the UK, cohort studies and comparative immunological studies have shown that exposure to environmental Mycobacterium tuberculosis can provide protection against tuberculosis and part of the BCG ineffectiveness is due in part to extensive heterogeneous exposure that masks vaccine effectiveness. The level of resistance has remained unchanged for more than two decades (<10%). Vaccination with Mycobacterium vaccae did not provide protection, but treatment with cotrimoxazole for HIV-positive patients reduced mortality. The Caron & Gabon project sheds light on the long-term population-based research to investigate the natural history of tuberculosis and the value of influencing tuberculosis control policies. Current research has focused on immunological markers of infection, disease and protection, focusing on elucidating the effect of antiretroviral therapy at the population level on the incidence of tuberculosis.